Beta-catenin (also known as cadherin-associated protein and β-Catenin) is a member of the catenin family of cytosolic proteins and a pivotal player in the signalling pathway initiated by Wnt proteins, mediators of several developmental processes. Beta-catenin undergoes phosphorylation upon growth factor stimulation resulting in reduced cell adhesion.
The role of beta-catenin in the development of cancer has been shown to be regulated by the expression product of the APC (adenomatous polyposis of the colon) gene. The APC tumor suppressor protein binds to beta-catenin, while beta-catenin was shown to interact with Tcf and Lef transcription factors. Morin et al. (Morin et al., Science, 1997, 275, 1787-1790) report that APC protein down-regulates the transcriptional activation mediated by beta-catenin and Tcf-4 in colon cancer. Their results indicate that the regulation of beta-catenin is critical to APC's tumor suppressive effect and that this regulation can be circumvented by mutations in either APC or beta-catenin.
Morin et al. showed that mutations of beta-catenin which affect phosphorylation sites rendered the cells insensitive to APC-mediated down-regulation of beta-atenin and that this disrupted mechanism was critical to colorectal tumorigenesis (Morin et al., Science, 1997, 275, 1787-1790).
Several studies report on the detection of mutations in beta-catenin in various cancer cell lines and abnormally high amounts of beta-catenin have been found in melanoma cell lines.
U.S. Pat. No. 6,066,500 to Bennett et al. describes antisense compounds, compositions and methods for modulating the expression of beta-catenin.
Considering the involvement of beta-catenin in the development of cancer, there remains a need for agents capable of effectively inhibiting beta-catenin function.